Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy

Andrea M. Vincent, James L. Edwards, Lisa L. McLean, Yu Hong, Federica Cerri, Ignazio Lopez, Angelo Quattrini, Eva L. Feldman

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondrial-mediated oxidative stress in response to high glucose is proposed as a primary cause of dorsal root ganglia (DRG) neuron injury in the pathogenesis of diabetic neuropathy. In the present study, we report a greater number of mitochondria in both myelinated and unmyelinated dorsal root axons in a well-established model of murine diabetic neuropathy. No similar changes were seen in younger diabetic animals without neuropathy or in the ventral motor roots of any diabetic animals. These findings led us to examine mitochondrial biogenesis and fission in response to hyperglycemia in the neurites of cultured DRG neurons. We demonstrate overall mitochondrial biogenesis via increases in mitochondrial transcription factors and increases in mitochondrial DNA in both DRG neurons and axons. However, this process occurs over a longer time period than a rapidly observed increase in the number of mitochondria in DRG neurites that appears to result, at least in part, from mitochondrial fission. We conclude that during acute hyperglycemia, mitochondrial fission is a prominent response, and excessive mitochondrial fission may result in dysregulation of energy production, activation of caspase 3, and subsequent DRG neuron injury. During more prolonged hyperglycemia, there is evidence of compensatory mitochondrial biogenesis in axons. Our data suggest that an imbalance between mitochondrial biogenesis and fission may play a role in the pathogenesis of diabetic neuropathy.

Original languageEnglish
Pages (from-to)477-489
Number of pages13
JournalActa Neuropathologica
Volume120
Issue number4
DOIs
Publication statusPublished - Oct 2010

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy'. Together they form a unique fingerprint.

Cite this